The objective of this umbrella project is the detailed understanding of the developmental program that culminates in myelin synthesis. We are particularly interested in obtaining molecular level information about the control of expression of the myelin basic protein gene and the proteolipid protein gene. To this end, we cDNA cloned and sequenced both human and mouse myelin basic protein mRNA and proteolipid protein mRNA. We used these characterized cDNAs to identify and study the organization of the genes encoding them. Our results demonstrate conclusively that the multiple forms of myelin basic protein which are found in both man and mouse originate from a mechanism of alternative splicing of the nascent gene transcript. Genes of two mutant mice have also been well characterized. The Shiverer mouse was found to have a massive deletion in the myelin basic protein gene, whereas the Jimpy mouse has a small deletion in the proteolipid protein gene. Consequently, neither mutant mouse is able to synthesize myelin and both mutants suffer from a neurological disease.